Kim Ki-Hye, Hwang Hye Suk, Lee Youri, Jung Yu-Jin, Ko Eun-Ju, Song Jae Min, Kang Sang-Moo
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea.
Virology. 2025 Nov;612:110674. doi: 10.1016/j.virol.2025.110674. Epub 2025 Sep 1.
To better understand the contribution of interferon-γ (IFN-γ) receptor signaling to vaccine-induced immunity, we employed A129 (IFN-α/β receptor-deficient) and AG129 (IFN-α/β/γ receptor-deficient) mouse models. AG129 mice induced comparable levels of virus-specific IgG after vaccination with influenza virus H5 hemagglutinin (HA) virus-like particles (VLPs). Vaccinated AG129 mice with HA VLPs exhibited impaired Th1-immune responses, lower hemagglutination inhibition (HAI) titers, increased susceptibility to virus infection, and lower survival rates following influenza virus (H5N1) challenge than vaccinated A129 mice. The AG129 mice also displayed defective germinal center and plasma cell responses, dysregulated lung inflammation with elevated pro-inflammatory cytokines and chemokines, impaired recruitment of monocytes, natural killer cells, and antigen-presenting cells after HA VLP vaccination and virus challenge, compared to A129 mice. Collectively, these findings underscore the critical role of IFN-γ signaling in coordinating effective and balanced immune responses to influenza HA VLP vaccination and conferring protection against virus infection.
为了更好地理解干扰素-γ（IFN-γ）受体信号传导对疫苗诱导免疫的贡献，我们采用了A129（IFN-α/β受体缺陷型）和AG129（IFN-α/β/γ受体缺陷型）小鼠模型。用甲型流感病毒H5血凝素（HA）病毒样颗粒（VLP）接种后，AG129小鼠诱导出了相当水平的病毒特异性IgG。与接种疫苗的A129小鼠相比，接种HA VLP的AG129小鼠表现出Th1免疫反应受损、血凝抑制（HAI）效价降低、对病毒感染的易感性增加以及甲型流感病毒（H5N1）攻击后的存活率降低。与A129小鼠相比，AG129小鼠在接种HA VLP疫苗和病毒攻击后，生发中心和浆细胞反应也存在缺陷，肺炎症失调，促炎细胞因子和趋化因子水平升高，单核细胞、自然杀伤细胞和抗原呈递细胞的募集受损。总的来说，这些发现强调了IFN-γ信号传导在协调对甲型流感HA VLP疫苗的有效和平衡免疫反应以及赋予抗病毒感染保护方面的关键作用。
